title: ClC-3 chloride channel prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through mitochondria dependent pathway.
abstract: ClC-3 Cl(-) channel plays an important role in cell volume regulation and cell cycle. In vascular smooth muscle cells, we have found that ClC-3 was involved in ET-1 induced cell proliferation. The present study was designed to further investigate the role of ClC-3 Cl(-) channel in H(2)O(2)-induced apoptosis and its underlying mechanisms in rat basilar arterial smooth muscle cell (BASMCs). By using ClC-3 cDNA and small interference RNA (siRNA) transfection strategy, it was found that overexpression of ClC-3 significantly decreased the apoptotic rate of H(2)O(2)-treated BASMCs and increased the cell viability, whereas silencing of ClC-3 with siRNA produced opposite effects and increased the apoptotic rate. ClC-3 overexpression decreased cytochrome C release and caspase-3 activation, and increased both the stability of mitochondrial membrane potential and the ratio of Bcl-2/Bax, whereas silencing of ClC-3 produced opposite effect. Furthermore, we demonstrated that overexpression of ClC-3 attenuated, whereas silencing of ClC-3 facilitated, the degradation of LaminA, one of the structural matrix proteins, in BASMCs. Our data suggest that ClC-3 Cl(-) channel can modulate H(2)O(2)-induced apoptosis in BASMCs via the intrinsic, mitochondrial pathway.
authors.affiliation: Department of Pharmacology, Cardiac and Cerebrovascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qian
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Du
authors.forename: Yong-Bo
authors.initials: YB
authors.lastname: Tang
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Lv
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001488:Basilar Artery / Q000166:cytology* / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D006861:Hydrogen Peroxide